Clinical characteristics of a familial inherited myxomatous valvular dystrophy mapped to Xq28

OBJECTIVES The purpose of this study was to describe the phenotypic charact eristics of an inherited myxomatous valvular dystrophy mapped to Xq28. BACKGROUND Myxomatous valve dystrophies are a frequent cause of valvular di seases, the most common being idiopathic mitral valve prolapse. They form a group of heterogeneous diseases difficult to subclassify. The first mappin g of the gene for a myxoid valvular dystrophy to Xq28 allowed investigation of the phenotype of affected members in a large family and characterizatio n of the disease. METHODS Among the 318 members in the pedigree, 89 agreed to participate in this study. Phenotypic characteristics were investigated using clinical exa mination, transthoracic echocardiography and biological analysis (F.VIII ac tivity). Genetic status was based on haplotype analysis. RESULTS Among 46 males, 9 were hemizygous to the mutant allele and had an o bvious mitral and/or aortic myxomatous valve defect, and 4 had undergone va lvular surgery. All had typical mitral valve prolapse associated in six cas es with moderate to severe aortic regurgitation. The valve defect cosegrega ted with mild hemophilia A (F.VIII activity 0.32 +/- 0.05). The 37 remainin g males had normal valves and normal F.VIII activity. Heterozygous women we re identified on the basis of their haplotypes. Among the 17 women heterozy gous to the mutant allele, moderate mitral regurgitation was present in 8, associated with mild mitral valve prolapse in 1 and aortic regurgitation in 3, whereas 2 women had isolated mild aortic regurgitant murmur. In heteroz ygotes, the penetrance value was 0.60 but increased with age. CONCLUSION X-linked myxomatous valvular disease is characterized by mitral valve dystrophy frequently associated with degeneration of the aortic valve s affecting males and, to a lower severity, females. The first localization of a gene for myxomatous valvular diseases is the first step for the subcl assification of these diseases. (J Am Coll Cardiol 2000;35:1890-7) (C) 2000 by the American College of Cardiology.